Effects of a microgravity environment on the crystallization of biological macromolecules

Macromolecules crystals are indispensable intermediates in the analysis of macromolecular structure, are essential for the application of x-ray diffraction methods, and are at the same time the greatest obstacle to success. Protein crystals are generally difficult to grow, often of imperfect form or small size, and frequently lack sufficient order. Their growth has become the rate limiting step in x-ray crystallography. Evidence has emerged from protein crystallization experiments carried out in space that suggests macromolecular crystals of improved order and quality can be grown in a microgravity environment. Presumably the absence of density driven convection and sedimentation permits a more deliberate and graceful entry of individual molecules into the crystal lattice. This in turn results in improvements in both morphology and the diffraction patterns of the crystals. The precise mechanisms for these improvements and the means for their optimization are, however, not understood at more than a rudimentary level. I attempt here to review microgravity effects that may play a role in protein crystal growth, sedimentation, convection and surface contact, and suggest their possible mechanisms.